Exercise tolerance and quality of life in patients with known or suspected coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is known to impact on patients' physical and mental health. The relationship between performance on treadmill exercise tolerance test (ETT) and health-related quality of life (HRQL)has never been specifically investigated in the setting of CAD. METHODS: Consecutive patients undergoing an ETT with the Bruce protocol during a diagnostic workup for CAD (n = 1,631, age 55 ± 12 years) were evaluated. Exercise-related indices were recorded. Detailed information on cardiovascular risk factors and past medical history were obtained. HRQLwas assessed with the use of the validated 36-Item Short Form Survey (SF-36) questionnaire. RESULTS: Increasing age and the presence of cardiovascular risk factors and comorbidities correlated with lower scores on the physical and mental health component of SF-36(all P < 0.05). Subjects with arrhythmias during exercise and slow recovery of systolic blood pressure had lower scores on the physical health indices or the Social Role Functioning component (P < 0.05). Achieved target heart rate and good exercise tolerance were independently associated with better scores of the physical and mental health domains of SF-36 and overall HRQLscores (ß = 0.05 for target HR and PCS-36, ß = 1.86 and ß = 1.66 per increasing stage of exercise tolerance and PCS-36 and MCS-36, respectively, P < 0.001 for all associations). Ischemic ECG changes were associated with worse scores on Physical Functioning (ß = - 3.2, P = 0.02) and Bodily Pain (ß = - 4.55, P = 0.026). CONCLUSION: ETT parameters are associated with HRQL indices in patients evaluated for possible CAD. Physical conditioning may increase patient well-being and could serve as a complementary target in conjunction with cardiovascular drug therapy.

Multiparametric Stress Echocardiography in the Diagnosis of IOCA and INOCA: Role of CFVR Measurement.

We present assessment of chest pain patients by multiparametric dobutamine stress echocardiography to differentiate inducible ischemia with obstructive coronary artery disease and with no obstructive coronary artery disease. In addition to the classical regional wall motion abnormality, we illustrate how coronary flow velocity reserve by Doppler echocardiography assists diagnosing coronary microvascular dysfunction. (Level of Difficulty: Advanced.).

The effect of atropine used in dobutamine stress echocardiography on pupil diameter.

BACKGROUND: The use of atropine during dobutamine stress echocardiography (DSE) is contraindicated in persons with narrow angle glaucoma though there is limited evidence that low doses of intravenous atropine do not cause pupillary dilation. OBJECTIVE: The aim of this study is to investigate whether atropine when administered in persons without glaucoma during dobutamine stress echocardiography causes pupillary dilation. METHODS AND RESULTS: Out of 144 patients without a history of glaucoma referred for DSE for clinical indications, 105 patients received intravenous atropine doses ranging from 0.1 mg to 1.25 mg (most patients received 0.25-0.75 mg). Pupil diameter of both eyes was measured under the same light conditions before and after the DSE using a CP-30 Optical Digital PD Ruler. For the total of 210 examined eyes pupil diameter remained unaltered after each DSE test (3.65 ± 0.799 mm before vs 3.63 ± 0.766 mm after, p = .737). Similarly, pupil diameter remained unchanged when left and right eyes were assessed separately (right eye: 3.770 ± 0.812 before vs 3.752 ± 0.745 mm after, p = .821 and left eye: 3.521 ± 0.770 before vs 3.499 ± 0.770 mm after, p = .806). Diameter of right and left pupil were also unaltered after grouping patients by sex and iris pigmentation. Age, weight, atropine dose and propranolol dose were not correlated with changes in pupil diameter. CONCLUSION: Intravenous atropine in usual doses administered in DSE does not cause mydriasis in adults without glaucoma. Future studies need to confirm our findings and expand the investigation regarding safety of atropine use during DSE in patients with narrow angle glaucoma.

Novel methodology for the detection of exercise-induced myocardial wall motion abnormalities by surface electrocardiogram during exercise test.

BACKGROUND: We investigated whether ischemia-induced wall motion abnormalities during exercise test modify electrical vector variation. METHODS: We performed treadmill exercise test and thallium 201 scintigraphy in 150 normotensives. Beat-to-beat change of direction of S wave in V(1) (reference lead) was compared with that of R wave in V(5) and aVF, representative of anterior and inferior walls, respectively. The percentage of neighboring QRS couples where S wave in V(1) and R wave in V(5) or aVF change toward the same direction (increase or decrease) constitutes V1-V5 and V1-aVF indexes. RESULTS: V1-V5 and V1-aVF indexes were significantly decreased in subjects with reversible anterior or inferior ischemia, respectively. A decrease in V1-V5 index ≥0.14 defines those with anterior wall ischemia (sensitivity, 100%; specificity, 75.5%), whereas a decrease in V1-aVF index ≥0.05 defines those with inferior wall ischemia (sensitivity, 92.3%; specificity, 61.5%). CONCLUSIONS: These novel electrocardiographic exercise test indexes improved significantly their sensitivities.

Correlation of ST-segment "hump sign" during exercise testing with impaired diastolic function of the left ventricle.

BACKGROUND: The appearance of a discrete upward deflection of the ST segment, termed the ST hump sign during exercise testing has been associated with resting hypertension and exaggerated blood pressure response to exercise. OBJECTIVE: We investigated the correlation between the presence of hump sign during exercise testing with coexisting impaired diastolic function of the left ventricle (LV) at these patients. METHODS: We formed a cohort of 237 nonconsecutive patients (140 males, 41 +/- 5 years old) having undergone a treadmill test, according to the Bruce protocol, which divided into 2 groups: group A, including 130 patients which presented ST-segment hump sign at any of the leads of the electrocardiograms recorded during exercise, and group B, including 107 patients that didn't. All patients subsequently underwent an echocardiographic estimation of the LV diastolic function, using conventional and Tissue Doppler Imaging techniques. RESULTS: From 237 patients included in our study, 106 had echocardiographic signs of diastolic LV dysfunction. Among them, the appearance of ST hump sign at the peak of exercise testing was observed in 93 patients (88%), particularly in the inferior and lateral leads, while no ST hump sign was observed only in 13 patients (12%) with impaired diastolic LV function. CONCLUSIONS: The appearance of ST segment hump sign during exercise testing is strongly correlated with diastolic LV dysfunction and can be used as an exercise electrocardiographic index of diastolic LV dysfunction, independently from the echocardiographic study.

Noninvasive Cardiac Output and Central Systolic Pressure From Cuff-Pressure and Pulse Wave Velocity.

GOAL: We introduce a novel approach to estimate cardiac output (CO) and central systolic blood pressure (cSBP) from noninvasive measurements of peripheral cuff-pressure and carotid-to-femoral pulse wave velocity (cf-PWV). METHODS: The adjustment of a previously validated one-dimensional arterial tree model is achieved via an optimization process. In the optimization loop, compliance and resistance of the generic arterial tree model as well as aortic flow are adjusted so that simulated brachial systolic and diastolic pressures and cf-PWV converge towards the measured brachial systolic and diastolic pressures and cf-PWV. The process is repeated until full convergence in terms of both brachial pressures and cf-PWV is reached. To assess the accuracy of the proposed framework, we implemented the algorithm on in vivo anonymized data from 20 subjects and compared the method-derived estimates of CO and cSBP to patient-specific measurements obtained with Mobil-O-Graph apparatus (central pressure) and two-dimensional transthoracic echocardiography (aortic blood flow). RESULTS: Both CO and cSBP estimates were found to be in good agreement with the reference values achieving an RMSE of 0.36 L/min and 2.46 mmHg, respectively. Low biases were reported, namely -0.04 ± 0.36 L/min for CO predictions and -0.27 ± 2.51 mmHg for cSBP predictions. SIGNIFICANCE: Our one-dimensional model can be successfully "tuned" to partially patient-specific standards by using noninvasive, easily obtained peripheral measurement data. The in vivo evaluation demonstrated that this method can potentially be used to obtain central aortic hemodynamic parameters in a noninvasive and accurate way.

Eligibility for PCSK-9 inhibitors treatment in acute coronary syndrome, chronic coronary artery disease and outpatient dyslipidemic patients.

BACKGROUND AND AIMS: We aimed to investigate potential eligibility for proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in patients with coronary artery disease and dyslipidaemia according to patient characteristics and variable criteria. METHODS: We prospectively enrolled 2000 patients (acute coronary syndrome = 407, chronic coronary artery disease inpatients = 1087, outpatient Lipid's clinic = 506). To calculate PCSK-9 inhibitors real-world eligibility, a proprietary adjustable software was developed, which stores data and patient characteristics and can determine eligibility depending on different criteria. We tested four scenarios with different LDL thresholds according to ESC/EAS 2016 and 2019 Guidelines, 2017 American College of Cardiology Expert Consensus, and National criteria. RESULTS: The eligible percentage was 18.85%, 9.75%, 8.55% and 2.15%, in the total population for the four classifications, respectively, and it varied according to clinical status. The increase toward more recent guidelines was mostly attributed to the increasing number of coronary patients who become eligible as our criteria become stricter. CONCLUSIONS: For the first time, a realistic estimation of PCSK-9 eligibility is provided via an adjustable predictive model in a population of 2000 patients with acute coronary syndrome, chronic coronary artery disease and dyslipidaemia. This can be a valuable tool for the incorporation of PCSK-9 inhibitors in health care systems.

Electrocardiographic criteria for detecting coronary artery disease in hypertensive patients with ST-segment changes during exercise testing.

PURPOSE: It is well known that patients with arterial hypertension frequently present with ischemic electrocardiographic changes during exercise testing without actually having coronary artery disease (CAD). The purpose of this study was to establish additional electrocardiographic criteria during exercise testing for detecting CAD in hypertensive patients with ischemic ST-segment response. METHODS: Three hundred eighty-two consecutive hypertensive patients (224 males, 58 +/- 8 years) who presented with ischemic electrocardiographic changes during exercise testing and agreed to undergo coronary arteriography were included in the study. RESULTS: From 382 hypertensive patients undergoing coronary angiography, only 76 (20%) had significant coronary stenosis, whereas 306 (80%) had normal coronary arteries. From 382 patients, 287 (75%) (group A) presented with ST-segment depression during exercise in leads II-III-aVF-V(6), 271 (94%) of which had normal arteries at the angiography. The remaining 95 patients (25%) (group B) of the studied patients presented with ST-segment depression in II-III-aVF and/or V(4) through V(6), 60 (63%) of which had CAD. Furthermore, 251 patients of group A presented with ST-segment depression during the fourth to sixth minute of the recovery period in V(4) through V(6), 247 (98%) of which had normal arteries. Another 28 patients from group B presented with ST-segment depression during the fourth to eighth minute of the recovery period in V(4) through V(6), 22 (79%) of which had significant coronary artery stenosis. CONCLUSIONS: Hypertensive patients who present with ST-segment depression during exercise in leads II-III-aVF and/or V(4) through V(6) and with a prolonged duration of this depression at the recovery phase (fourth to eighth minute) are more likely to have CAD. Absence of ST-segment depression in V(4) and V(5) at the end of exercise or during the seventh and eighth minute of recovery favors a false-positive result.

Assessment of arterial baroreflex sensitivity by different computational analyses of pressure wave signals alone.

BACKGROUND AND OBJECTIVE: Baroreflex sensitivity (BRS) is an important indicator of the functionality of the arterial baroreceptors, and its assessment may have major research and clinical implications. An important requirement for its quantification is the continuous recording of electrocardiography (ECG) signal, so as to extract the RR interval, in parallel with continuous beat-to-beat blood pressure recording. We aimed to accurately calculate the RR Interval from pressure wave recordings per se, namely, the Pulse Interval (PI) using various arterial pulse wave analysis algorithms and to evaluate the precision and accuracy of BRS values calculated with the PI compared to BRS values calculated with the RR Interval. METHODS: We analyzed the open access data of the Eurobavar study, which contains a set of ECG and arterial blood pressure (BP) wave signals recorded at 11 European centers. Pressure waveforms were continuously recorded by the Finapres apparatus which uses a finger cuff. The cuff pressure around the finger is dynamically adjusted by a servo-system to equal intra-arterial pressure, thus allowing the continuous recording of beat-to-beat BP waves. RR Interval was calculated from the ECG, whereas, PI was extracted from the arterial pulse waveforms, using 4 different methods (minimum, maximum, maximum 1st derivative and intersecting tangents method). BRS values were estimated by time domain and frequency domain methods. In order to compare agreement, accuracy, precision, variability, and the association between the reference BRS using the RR Interval and the BRS values using PI, standard statistical methods (i.e. intraclass correlation coefficients, RMSE, regression analysis) and Bland-Altman methods were performed. RESULTS: We found that analysis of pressure waves alone by frequency-based (i.e. spectral) methods, provides the most accurate results of BRS estimation compared to time-domain methods (ICC > 0.9, R > 0.9, RMSE > 0.8 ms/mmHg). Concerning the spectral method, any algorithm for PI calculation is sufficient, as all show excellent agreement with the respective RR-intervals determined by ECG time series. Only the intersecting tangents and the maximum 1st derivative methods for PI calculation produce the most accurate results in time domain BRS estimation. CONCLUSION: BRS estimation by proper analysis of pressure wave signals alone is feasible and accurate. Further studies are needed to investigate the clinical validity and relevance of the different BRS estimations in diagnostic, prognostic and therapeutic levels.

Blood Pressure Deviation from the Golden Ratio φ and All-cause Mortality: A Pythagorean View of the Arterial Pulse.

INTRODUCTION: There is one mathematical element with strong historical and philosophical background that exhibits remarkable properties and applications; the golden ratio (phi). Mathematically, the golden ratio equals approximately 1.61803. A rather provocative geometrical analysis of the arterial pulse according to the golden ratio was recently described, and herein, we aim to set out the hypothesis that individuals with blood pressure (BP) values that follow the golden ratio may have different prognosis than those whose BPs deviate from the divine proportions. MATERIALS AND METHODS: We used published data from the National Health and Nutrition Examination Survey during 1999-2010. RESULTS: We found that the deviation of the BP values from the golden ratio is independently associated with all-cause mortality. CONCLUSIONS: This observation stimulates further research of the potential utility of the golden ratio of BP values on the diagnosis and prediction of BP-related abnormalities and risk.

Correlation of modification of heart rate recovery with adaptation to myocardial ischemia in a model of sequential exercise testings.

BACKGROUND: Heart rate recovery (HRR) has been identified as a reliable predictor of cardiac mortality, correlated with autonomic tone. In a model of sequential exercise testings, we investigated the reproducibility of HRR and the association between HRR modification and myocardial adaptation to ischemia. METHODS: We studied 128 patients (mean age 62 +/- 9 years, 83% males) with angiographically documented coronary artery disease (CAD) and a first positive exercise testing, who agreed to undergo a second exercise testing after 24 hours. RESULTS: HRR was increased from 25 +/- 10 beats/min at the first exercise testing to 30 +/- 13 beats/min at the second exercise testing (P < 0.001). Thereafter, participants were divided into two groups: Group I comprised 88 patients who presented augmentation of the HRR in the first compared to the second exercise testing, while group II comprised 40 patients who presented unchanged or reduced HRR. The rate-pressure product (RPP) at 1 mm ST-segment depression (ischemic threshold) at the second compared to the first exercise testing were significantly improved in group I patients (2345 +/- 3429 mmHg/min), while it was worsened in group II patients (-630 +/- 2510 mmHg/min) (P < 0.001). CONCLUSIONS: In a model of sequential exercise testings, myocardial adaptation to exercise-induced ischemia was associated with favorable modification of HRR.

QRS score improves diagnostic ability of treadmill exercise testing in women.

OBJECTIVE: The accuracy of treadmill exercise testing to detect coronary artery disease is limited in women. This study was undertaken to evaluate whether QRS score can improve the accuracy of treadmill exercise testing in women. METHODS: The study population consisted of 114 women with angina-like symptoms, who underwent both treadmill exercise testing and coronary angiography. The impact of QRS score on the standard ST-segment based diagnostic ability of treadmill exercise testing to detect coronary artery disease was studied. RESULTS: Incorporation of QRS score in standard ST-segment diagnostic criteria significantly enhanced sensitivity (from 59 to 80%), specificity (from 40 to 94%) and diagnostic accuracy (from 50 to 87%) of treadmill exercise testing. The QRS score was shown to reduce significantly the false-positive results from 60 to 6%. Furthermore, QRS score accuracy was correlated with the extent of coronary artery disease. The diagnostic ability of QRS score was greater both among patients with normal and impaired systolic function of the left ventricle. CONCLUSIONS: QRS score can improve the limited diagnostic accuracy of treadmill exercise testing in women, by predominantly decreasing the high prevalence of false-positive results.

Engineering 'Posthumans': To Be or Not to Be?

Emerging technological innovations have transformed some science fiction ideas into reality, promising radical changes in human nature. New philosophical and intellectual movements such as 'transhumanism' and 'posthumanism' try to foretell and even direct the future of our existence while dealing with new and complex ethical, social, political issues and dilemmas.

Exercise capacity and haemodynamic response among 12,327 individuals with cardio-metabolic risk factors undergoing treadmill exercise.

Aims Haemodynamic parameters during and after exercise test seem to have a role in predicting cardiovascular events. We sought to evaluate the potential different responses in exercise capacity, heart rate and blood pressure levels in relation to major cardiovascular disease risk factors, among individuals undergoing exercise tolerance testing. Methods and results Consecutive individuals ( N = 12,327), aged 55 ± 11.8 years, underwent exercise tolerance testing, using the Bruce protocol. Obese participants showed higher values of peak systolic and diastolic blood pressure ( p < 0.01), with no heart rate differences. Diabetic patients presented increased systolic blood pressure across the test ( p = 0.02) and decreased tolerance to exercise ( p = 0.05), but without differences in diastolic blood pressure or heart rate. Hypertensives showed exaggerated blood pressure, chronotropic response and decreased capacity to exercise ( p < 0.001 for all). Smokers had increased baseline systolic blood pressure, peak diastolic blood pressure and recovery heart rate and decreased tolerance to exercise ( p < 0.001 for all). For all high-risk subgroups, exercise testing was more often positive. Age-stratified analysis revealed different patterns: all four risk factors significantly decreased peak metabolic equivalent in subjects <50 years old ( p < 0.05 for all), while in participants between 50 and 69 years old, diabetes mellitus ( p = 0.03), hypertension ( p = 0.04) and smoking ( p = 0.01) predicted achieved metabolic equivalent. For patients of ≥ 70 years old, obesity ( p = 0.006) and hypertension ( p = 0.02) decreased peak metabolic equivalent and systolic blood pressure recovery. In subjects without pre-existing cardiovascular disease and negative exercise tolerance testing (7064 subjects, mean age: 52.4 ± 12.1 years, 62.9% males), age, obesity, hypertension and female gender inversely and independently predicted peak metabolic equivalent. Conclusions High-risk individuals showed different haemodynamic responses when undergoing exercise tolerance testing, reflecting independent pathophysiological pathways.

Quantification of new structural features of coronary plaques by computational post-hoc analysis of virtual histology-intravascular ultrasound images.

Cardiovascular disease and complications are often mediated by the development and rupture of atherosclerotic plaques. Plaque composition is a major factor that determines plaque vulnerability. Intravascular ultrasound (IVUS) and spectral analysis of the radio frequency signal provide an in vivo tissue characterisation of atherosclerotic plaques, known as virtual histology (VH-IVUS). In VH-IVUS analysis, four histological tissue components are classified: fibrous, fibro/fatty, necrotic core and calcium. Existing technology determines only the area of each component within the plaque. Quantitative, objective characterisation of other plaque components' patterns within the plaque is lacking. The aim of this study was to determine new compositional and structural indices which indicate spatial distribution, heterogeneity and dispersity of each VH-IVUS-derived component within the plaque area and also with respect to the plaque-lumen border. We developed an automated computational system in Java for the analysis of both single cross-sectional segments and the whole length of the examined plaque (volumetric analysis). The following parameters were computed: the number of different solid segments and the area of the largest solid segment of each component within the plaque, the per cent of the lumen border that is surrounded by each component, the number of different solid segments and the largest area of a solid segment of each component that adjoins the lumen border. Especially components' localisation in relation to the lumen border may significantly influence plaque vulnerability and plaque-stent interaction, which should be investigated in future clinical studies.

First in vivo application and evaluation of a novel method for non-invasive estimation of cardiac output.

Surgical or critically ill patients often require continuous assessment of cardiac output (CO) for diagnostic purposes or for guiding therapeutic interventions. A new method of non-invasive CO estimation has been recently developed, which is based on pressure wave analysis. However, its validity has been examined only in silico. Aim of this study was to evaluate in vivo the reproducibility and accuracy of the "systolic volume balance" method (SVB). Twenty two subjects underwent 2-D transthoracic echocardiography for CO measurement (reference value of CO). The application of SVB method required aortic pressure wave analysis and estimation of total arterial compliance. Aortic pulses were derived by mathematical transformation of radial pressure waves recorded by applanation tonometry. Total compliance was estimated by the "pulse pressure" method. The agreement, association, variability, bias and precision between Doppler and SVB measures of CO were evaluated by intraclass correlation coefficient (ICC), mean difference, SD of differences, percentage error (PR) and Bland-Altman analysis. SVB yielded very reproducible CO estimates (ICC=0.84, mean difference 0.27 ± 0.73 L/min, PR = 16.7%). SVB-derived CO was comparable with Doppler measurements, indicating a good agreement and accuracy (ICC = 0.74, mean difference = -0.22 ± 0.364 L/min, PR ≈ 15). The basic mathematical and physical principles of the SVB method provide highly reproducible and accurate estimates of CO compared with echocardiography.

The significance of right-sided chest leads in exercise testing for the detection of right ventricular dysfunction post myocardial infarction of the inferior wall.

BACKGROUND: The incorporation of right-sided chest leads (V(3)R-V(5)R) into the standard exercise testing has been reported to improve its diagnostic accuracy. The purpose of this study was to evaluate the ability of exercise testing in detecting right ventricular (RV) dysfunction post myocardial infarction (MI) of the inferior wall, using additional V(3)R-V(5)R leads. METHODS: We studied 133 patients (59 ± 5 years, 81 males) with a history of inferior MI due to right coronary artery obstruction (affirmed with coronary angiography). All patients underwent an echocardiographic assessment of RV function 4 weeks after discharge and an exercise treadmill test in order to detect possible RV dysfunction. Recordings during exercise were obtained with the standard 12 leads plus V(3)R-V(5)R. RESULTS: From 133 patients, 97 (group A) presented with normal right ventricle according to the echocardiographic study while the rest 36 patients (group B) presented with RV dysfunction. Maximal exercise-induced ST-segment deviation (in mm) was similar in the standard 12 leads for the 2 groups (2.1 ± 0.4 vs 1.8 ± 0.3, p = NS) while in V(3)R-V(5)R it was greater in group B (0.7 ± 0.3 vs 1.4 ± 0.4, p<0.05). Sensitivity, positive prognostic value, negative prognostic value and accuracy of exercise testing in detecting RV dysfunction were all improved using V(3)R-V(5)R (78 vs 47%, 39 vs 29%, 87 vs 75%, 62 vs 55% respectively, p<0.05 for all) while specificity was not deteriorated (56 vs 58%, p = NS). CONCLUSIONS: The addition of right-sided chest leads (V(3)R-V(5)R) improves the diagnostic ability of standard exercise testing in detecting and especially in excluding RV dysfunction post inferior MI.

ST-Segment Depression in Hyperventilation Indicates a False Positive Exercise Test in Patients with Mitral Valve Prolapse.

Objectives. Mitral valve prolapse (MVP) is a known cause for false positive exercise test (ET). The purpose of this study was to establish additional electrocardiographic criteria to distinguish the false positive exercise results in patients with MVP. Methods. We studied 218 consecutive patients (53 ± 6 years, 103 males) with MVP (according to echocardiographic study), and positive treadmill ET was performed due to multiple cardiovascular risk factors or angina-like symptoms. A coronary angiography was performed to detect coronary artery disease (CAD). Results. From 218 patients, 90 (group A) presented with normal coronary arteries according to the angiography (false positive ET) while the rest 128 (group B) presented with CAD. ST-segment depression in hyperventilation phase was present in 54 patients of group A (60%) while only in 14 patients of group B (11%), P < .05. Conclusions. Presence of ST-segment depression in hyperventilation phase favors a false positive ET in patients with MVP.

Duration of treadmill exercise testing combined with QRS score predicts adverse cardiac outcome at long-term follow-up.

OBJECTIVE: Total exercise duration and abnormal QRS score values are treadmill exercise testing (TET) prognostic parameters that have been shown to be significantly and independently associated with cardiac mortality. We evaluated the prognostic value of a new index (M score, Michaelides score) incorporating TET duration and QRS score values in a simple index. METHODS: In this study, we included 626 patients, who underwent TET and coronary arteriography. Cardiac catheterization showed the presence of coronary artery disease in 64.3% of these patients. The M score was calculated by adding the value of the Athens QRS score to the duration of TET (in minutes). The outcome measure was a composite of myocardial infarction or death. Patients were prospectively followed for 38+/-21 months (median 36 months). RESULTS: The composite endpoint was more frequent among the patients of the 1st quartile (M-score values <-5.8). In univariate analysis, mortality of the first-quartile patients was significantly higher (14 vs. 1.1%, P<0.001). In multivariate Cox's regression analysis for age, sex, diabetes, smoking status, hypertension, hypercholesterolemia, maximum ST depression at TET, angina during TET, coronary artery disease on angiography, and echocardiographic left ventricular ejection fraction, the first quartile of M-score values was found to be independently associated with the composite endpoint (relative risk = 3.26, 95% confidence interval = 2.01-5.29, P<0.001). CONCLUSION: This study shows that a new index termed the M score, which incorporates QRS score and exercise duration, predicts mortality and occurrence of myocardial infarction at long-term follow-up of high-risk individuals, independently of TET-induced ST-segment changes.